Eye movement desensitization and reprocessing (EMDR) therapy or supportive counseling prior to exposure therapy in patients with panic disorder: study protocol for a multicenter randomized controlled trial (IMPROVE).

BACKGROUND: Exposure-based therapy is the treatment of choice for anxiety disorders, but many patients do not benefit sufficiently from it. Distressing images of threat related to the future or past may maintain the anxiety symptomatology or impede exposure therapy. An intervention that targets threat-related imagery is eye movement desensitization and reprocessing (EMDR) therapy. The main goal of this multicenter randomized controlled trial is to investigate whether EMDR therapy plus exposure therapy, relative to supportive counseling plus exposure therapy, improves treatment efficacy, tolerability, and adherence in patients with panic disorder. In addition, we will examine potential predictors of optimal treatment allocation, mechanisms of change as well as the long term effects of treatment. Finally, we will assess cost-effectiveness. METHODS: A multicenter randomized controlled trial mixed design will be conducted. Participants will be 50 patients, aged ≥ 18, diagnosed with a panic disorder. They will be randomly assigned to one of two conditions: EMDR therapy (i.e., flashforward strategy) or supportive counseling (each consisting of four weekly sessions of 90 min each) prior to exposure therapy (consisting of eight weekly sessions of 90 min each). Assessments will be made pre-treatment (T1), between-treatments (T2), post-treatment (T3), one month post-treatment (FU1) and six months post-treatment (FU2) by an assessor blind to treatment condition. The primary outcome measure is severity of panic-related symptoms. Secondary outcome measures are: tolerability of exposure therapy (initial avoidance, willingness to start exposure therapy, considered drop-out; no-show and drop-out), related symptomatology (generalized anxiety, depression), and functional impairment. DISCUSSION: The primary goals of this research are to compare the efficacy, tolerability, and adherence of EMDR therapy plus exposure therapy and supportive counseling plus exposure therapy and to identify predictors, moderators, and mediators for treatment success. This multi-center research aims to make a significant contribution to our understanding as to how treatment for patients with anxiety disorders can be optimized, and elucidate who can benefit most from this novel approach. TRIAL REGISTRATION: ISRCTN-ISRCTN29668369: Improving anxiety treatment by modifying emotional memories before real-life exposure. Registered 27 June 2022-retrospectively registered. ISRCTN-ISRCTN29668369.

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study.

AIMS: We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms. METHODS: Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up. RESULTS: The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder. CONCLUSION: Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.

Incremental Validity of Cognitive-Behavioral Therapy and Acceptance and Commitment Therapy Mechanisms for Anxiety and Panic Symptomology.

Background: acceptance and commitment therapy (ACT) and cognitive-behavioral therapy (CBT) are empirically supported treatments for anxiety and panic disorder (PD), though they differ in their putative vulnerability and maintenance processes. The present study examined the incremental validity of several of these models' proposed core processes, including anxiety sensitivity (AS), dispositional avoidance, experiential avoidance (EA), cognitive fusion (CF), and mindfulness, as well as the interaction of the processes within each model, in the prediction of anxiety and panic symptomology. Methods: a sample of US adults (n = 316) completed self-report measures of AS, dispositional avoidance, EA, CF, mindfulness, anxiety, and PD symptoms. A series of hierarchical multiple regression analyses were conducted. Results: hierarchical regression analyses indicated that AS, dispositional avoidance, and EA predicted anxiety and panic symptoms even after controlling for one another, CF, mindfulness, and demographic variables. Although mindfulness and CF was correlated with anxiety and panic at the univariate level, they did not predict either outcome above and beyond AS, dispositional avoidance, and EA. When interaction terms were added to the models, the interaction between AS and -dispositional avoidance was a significant predictor of panic and anxiety symptoms, whereas the interaction between EA and CF only predicted panic symptoms. None of the interactions that included mindfulness were significant predictors. Conclusions: these findings provide support the independent and interactive predictive value of traditional CBT (AS, dispositional avoidance, and AS-dispositional avoidance) and ACT (EA) processes for anxiety and panic symptoms, but raise questions about the incremental predictive utility of CF and mindfulness.

Effect of a slow-paced breathing with heart rate variability biofeedback intervention on pro-inflammatory cytokines in individuals with panic disorder - A randomized controlled trial.

A generalized proinflammatory state has been observed in individuals with panic disorder (PD). There is evidence that slow-paced breathing (SPB) with heart rate variability-biofeedback (HRV-BF) strengthens the nervus vagus with its anti-inflammatory pathway. Therefore, with this randomized controlled trial we aimed to investigate the effect of a four-week SPB with HRV-BF intervention on pro-inflammatory cytokines in people with PD. Fifty-five individuals with PD (mean age: 37.22 ± 15.13 years) were randomly allocated either to SPB-HRV-BF (intervention group) or to HRV-Sham-BF (active control group). SPB-HRV-BF was performed over four weeks while cytokine concentration and HRV during a short-term resting condition were measured before and after intervention. SPB-HRV-BF decreased concentration of Tumor Necrosis Factor alpha (TNF-alpha) (F(1, 53) = 4.396, p ≤ .05, η2 = 0.077) in individuals with PD. In addition, SPB-HRV-BF demonstrated an increase in the HRV-time and frequency domain parameters SDNN, Total Power and LF during short-term resting condition. There was no intervention effect in HRV-Sham-BF group. In conclusion, SBP-HRV-BF as a non-pharmacological treatment may reduce pro-inflammatory cytokine TNF-alpha via the cholinergic anti-inflammatory pathway in individuals with PD. Based on the generalized proinflammatory state in PD, decreasing TNF-alpha is highly beneficial to reduce risk of cardiovascular diseases and metabolic syndrome.

Development of a brain wave model based on the quantitative analysis of EEG and EEG biofeedback therapy in patients with panic attacks during the COVID-19 pandemic.

The current global crisis facing the world is the COVID-19 pandemic. Infection from the SARS-CoV-2 virus leads to serious health complications and even death. As it turns out, COVID-19 not only physically assails the health of those infected, but also leads to serious mental illness regardless of the presence of the disease. Social isolation, fear, concern for oneself and one's loved ones, all of this occurs when a pandemic overloads people. People exhibit numerous neurological disorders that have never happened to them before. Patients are diagnosed with frequent panic attacks, the result of which can be seen in their Quantitative Electroencephalogram results. This test may be one of the main diagnostic tools of the COVID-19 pandemic. From the results obtained, it is possible to compare and draw conclusions. This method of testing effectively allows EEG biofeedback training and observes its effect on brain activity. The feedback received in this way gives us the opportunity to properly tailor a protocol for the patient and their conditions. Numerous studies support the effectiveness of EEG biofeedback for panic attacks and other psychiatric disorders. The purpose of our study was to show the effectiveness of EEG biofeedback with a Quantitative Electroencephalogram of the brainwave pattern after having COVID-19 and what symptoms may result.

Effect of a Biofeedback Intervention on Heart Rate Variability in Individuals With Panic Disorder: A Randomized Controlled Trial.

OBJECTIVE: Some individuals with panic disorder (PD) display reduced heart rate variability (HRV), which may result in an increased risk of cardiovascular mortality. Heart rate variability-biofeedback (HRV-BF) training has been shown to improve the modulation of the autonomic activity. Therefore, this randomized controlled trial was conducted to investigate the effect of a 4-week HRV-BF intervention in individuals with PD. HRV-BF training improved the modulation of the autonomic activity. Therefore, with this randomized controlled trial, we aimed to investigate the effect of a 4-week HRV-BF intervention in people with PD. METHODS: Thirty-six women and 16 men with PD (mean age = 35.85 [15.60] years) were randomly allocated either to HRV-BF with 0.1-Hz breathing as intervention group or to HRV-Sham-BF as active control group. HRV-BF was performed for 4 weeks, whereas HRV was measured both during a short-term resting condition and during a paced breathing condition before and after intervention. RESULTS: HRV-BF with 0.1-Hz breathing increased HRV and reduced panic symptoms in individuals with PD. HRV-BF with 0.1-Hz breathing demonstrated an increase in the time and frequency domain parameters of HRV during the short-term resting condition (ΔPost-Pre root mean square successive differences: 5.87 [14.03] milliseconds; ΔPost-Pre standard deviation of all NN intervals: 11.63 [17.06] milliseconds; ΔPost-Pre total power: 464.88 [1825.47] milliseconds2; ΔPost-Pre power in low-frequency range 0.04-0.15 Hz: 312.73 [592.71] milliseconds2), a decrease in the heart rate during the paced breathing condition (ΔPost-Pre: -5.87 [9.14] beats/min), and a decrease in the Panic and Agoraphobia Scale (ΔPost-Pre: -3.64 [6.30]). There was no intervention effect in the HRV-Sham-BF group. CONCLUSIONS: HRV-BF as a noninvasive and nonpharmacological treatment seems to be an important intervention option to improve reduced HRV and decrease panic symptoms in individuals with PD. Future studies are needed to establish whether these effects translate to reductions in the risk of cardiovascular disease in PD.

Early Trauma Is Associated With Suicidal Ideation in Patients With Panic Disorder.

ABSTRACT: There are several predictors of suicidality in patients with panic disorder (PD). Being a woman, younger age, low education level, unmarried status, and symptom severity have been suggested. This study aimed to examine whether early trauma is associated with suicidal ideation in patients with PD. Our study included 267 patients with PD and 105 controls. Data on sociodemographic variables and data from the Early Trauma Inventory Self Report-Short Form, Beck Depression Inventory, Panic Disorder Severity Scale, Anxiety Sensitivity Inventory-Revised, Coping Scales, and Scale for Suicide Ideation were collected, and correlation and regression analyses were performed. This study suggests that clinicians should consider early trauma when assessing suicidal ideation in patients with PD. Clinicians could consider alternative treatments, such as trauma-focused cognitive-behavioral therapy, eye movement desensitization, reprocessing approaches, and classical pharmacological and psychological treatments for patients with PD who have a history of early trauma and are expected to be at high risk for suicide.

[Professor CHEN Gui-zhen's experience of acupuncture for perimenopausal panic disorder].

Professor CHEN Gui-zhen's experience of acupuncture for perimenopausal panic disorder was summarized. Professor CHEN believes that the etiology and pathogenesis of perimenopausal panic disorder are the deficiency of congenital kidney essence and the injury of acquired spleen and stomach, leading to mental dysfunction. The clinical treatment should be based on the principle of "nourishing the congenital, tonifying the acquired, and regulating thoroughfare vessel and conception vessel". As for the acupoint selection, the combination of back-shu point and the front-mu point is valued; as for the acupuncture technique, quick needling and skillful application of catgut embedding are recommended. The combination of acupuncture and medicine shows synergistic effect. In addition, emotional therapy is also applied for this condition. In conclusion, it is advocated to treat perimenopausal panic disorder with the combination of acupuncture, catgut embedding, herbs and emotional therapy.

Ideomotor hypnoanalysis -value in uncovering significant subconscious memories in some psychiatric disorders.

Some patients with psychiatric disorders respond poorly to treatment. Case reports are presented to show the value of ideomotor hypnoanalysis as an augmentation assessment technique in psychiatric disorders like Depressive Disorders, Panic Disorders, Illness Anxiety Disorders, Post Traumatic Stress Disorders and Somatic Symptom Disorders. The use of ideomotor hypnoanalysis may be of great clinical value in uncovering subconscious imprints, past traumas, sensitizing, and precipitating memories.

Treatment of panic disorder by trigeminal nerve manipulation: A case series.

This is a report on two cases of patients with acute severe panic disorder relieved of their symptoms by manual manipulations of the trigeminal nerve's alveolar branches. The manipulations were performed via the oral cavity during one session, or two consecutive sessions less than a week apart. No other effective treatment was administered prior, concurrently or since the time of the treatment. The recovery from panic disorder was immediate and lasted for the entire period of observation of three years. The authors used the same procedure and achieved identical clinical results treating ten other clients over a period of three years. This was not a planned experiment or randomized study. Rather, this report presents clinical evidence and the authors' hypothesis based on clinical data and literature review.

In vivo investigation on bio-markers of perimenopausal panic disorder and catgut embedding acupoints mechanism.

BACKGROUND: Panic disorder (PD), defined by repeated and unexpected panic attacks, severely affects patients' living quality and social function. Perimenopausal women are high-risk group of PD and suffer greatly from it. Modern medicine therapies for this disorder have many side reactions and poor effects, so nonpharmacological modality is an urgent need. Although acupoint catgut embedding is widely used in clinical practice, there is no persuasive evidence of its effect for perimenopausal PD. The aim of this study is to investigate the effectiveness and safety of acupoint catgut embedding for perimenopausal PD and to elucidate the correlations among brain neural activation, bio-markers (amino acids) and clinical outcomes with radiographic evidence, thus to explore its neural mechanism. METHODS: The parallel designed, exploratory randomized controlled trial will include 70 outpatients with perimenopausal PD recruited from two hospitals of Chinese Medicine. These subjects will be randomly allocated to an intervention group (Group Embedding) and a control group (Group Medication) in a 1:1 ratio. The subjects in the intervention group will receive acupoint catgut embedding treatment two weeks a time in the following predefined acupuncture points: Shenshu (BL23), Sanyinjiao (SP6), Guanyuan (RN4), Ganshu (BL18), Zusanli (ST36) and Pishu (BL20). The included women of the control group will take 0.4 mg Alprazolam tablet orally, 1 tablet a time, 3 times a day. There is a study period of 3 months and a follow-up period of 1 month for each group. The primary outcomes will be the following therapeutic indexes: the frequency of panic attack, Panic Disorder Severity Score (PDSS), and Panic-associated Symptoms Score (PASS) during the observation period and follow-up period. The changes in Hamilton Anxiety Scale (HAMA) Score and Symptom Checklist 90 (SCL-90) Score will also be compared between these two groups. Additionally, functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) scans will be done before and after the observation period to show cranial neuroimaging changes. DISCUSSION: We present a study design and rationale to explore the effectiveness and neural mechanism of acupoint catgut embedding for perimenopausal PD. There are still several factors restrict our research such as no unified standard of diagnostic criteria and curative effect evaluation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-16009724, registered in November 2016.

Evaluating the Impact of Freespira on Panic Disorder Patients' Health Outcomes and Healthcare Costs within the Allegheny Health Network.

Panic disorder (PD) is a debilitating condition that drives medical spending at least twice as high as medically matched controls. Excessive utilization of healthcare resources comes from emergency department (ED), medications, diagnostic testing, and physician visits. Freespira is an FDA-cleared digital therapeutic that treats PD and panic attacks (PA) by correcting underlying abnormal respiratory physiology. Efficacy of Freespira has been established in prior studies. This paper reports on a quality improvement program that investigated whether treating PD patients with Freespira would reduce medical costs and improve outcomes over 12-months. Panic symptoms were assessed using the Panic Disorder Severity Scale (PDSS). Pre-and post-treatment insurance claims determined costs. At baseline, mean Clinician Global Impression (CGI-S) was 4.4 (moderately/markedly ill), mean PDSS was 14.4 and mean PA frequency/week was 2 (range 0-5). Immediately post-treatment (week 5) mean CGI-S, PDSS and weekly PA frequency declined to 2.8 (borderline/mildly ill, 4.9 (remission) and 0.2 (range 0-2) respectively, p < 0.001. 82% reported PDSS decrease of ≥ 40% (clinically significant), 86% were PA-free. One-year post treatment mean CGI-S, PDSS and PA remained low at 2.1, 4.4, and 0.3 (range 0-1) respectively. 91% had PDSS decrease of ≥ 40%, 73% were PA-free. The majority of patients were panic attack free and/or reduced their symptoms and avoidance behaviors 1-year post Freespira treatment. Mean overall medical costs were reduced by 35% from $548 to $358 PMPM (per member per month) or an annual reduction of $2280. at 12 months post-treatment. There was a 65% reduction in ED costs from $87 to $30 PMPM. Median pharmacy costs were reduced by 68% from $73 to $23 PMPM.

Anterior hippocampal volume predicts affect-focused psychotherapy outcome.

BACKGROUND: The hippocampus plays an important role in psychopathology and treatment outcome. While posterior hippocampus (PH) may be crucial for the learning process that exposure-based treatments require, affect-focused treatments might preferentially engage anterior hippocampus (AH). Previous studies have distinguished the different functions of these hippocampal sub-regions in memory, learning, and emotional processes, but not in treatment outcome. Examining two independent clinical trials, we hypothesized that anterior hippocampal volume would predict outcome of affect-focused treatment outcome [Interpersonal Psychotherapy (IPT); Panic-Focused Psychodynamic Psychotherapy (PFPP)], whereas posterior hippocampal volume would predict exposure-based treatment outcome [Prolonged Exposure (PE); Cognitive Behavioral Therapy (CBT); Applied Relaxation Training (ART)]. METHODS: Thirty-five patients with posttraumatic stress disorder (PTSD) and 24 with panic disorder (PD) underwent structural magnetic resonance imaging (MRI) before randomization to affect-focused (IPT for PTSD; PFPP for PD) or exposure-based treatments (PE for PTSD; CBT or ART for PD). AH and PH volume were regressed with clinical outcome changes. RESULTS: Baseline whole hippocampal volume did not predict post-treatment clinical severity scores in any treatment. For affect-focused treatments, but not exposure-based treatments, anterior hippocampal volume predicted clinical improvement. Smaller AH correlated with greater affect-focused treatment improvement. Posterior hippocampal volume did not predict treatment outcome. CONCLUSIONS: This is the first study to explore associations between hippocampal volume sub-regions and treatment outcome in PTSD and PD. Convergent results suggest that affect-focused treatment may influence the clinical outcome through the 'limbic' AH, whereas exposure-based treatments do not. These preliminary, theory-congruent, therapeutic findings require replication in a larger clinical trial.

Predictors of outcome in guided self-help cognitive behavioural therapy for common mental disorders in primary care.

Cognitive behavioural therapy (CBT) can effectively treat common mental disorders (CMDs), but access to treatment is insufficient. Guided self-help (GSH) CBT has shown effects comparable to face-to-face CBT and may be a resource-efficient treatment alternative. However, not all patients respond to GSH. Learning more about predictors of outcome may increase knowledge regarding which patients respond to GSH. The aim of this study was to investigate predictors of outcome for GSH CBT for patients with CMDs in primary care. Consecutive patients (N = 396) with a principal disorder of depression, anxiety, insomnia or stress-related disorders were included. All patients received GSH CBT. Outcomes were remission status, reliable change and post-treatment depression ratings. Predictors investigated were clinical, demographic and therapy-related variables. Analyses were conducted using logistic and linear regression. Higher educational level predicted remission, higher quality of life ratings predicted remission and decreased depression, and higher age at onset predicted reliable change. Therapy-related variables, i.e. patient adherence to treatment and patients' and clinicians' estimation of treatment response, were all related to outcome. More large-scale studies are needed, but the present study points at the importance of therapy-related variables such as monitoring and supporting treatment adherence for an increased chance of remission.

Effectiveness of mindfulness-based cognitive therapy in patients with anxiety disorders in secondary-care settings: A randomized controlled trial.

AIM: The primary objective of this study was to examine the effectiveness of mindfulness-based cognitive therapy (MBCT) in secondary-care settings where the vast majority of the patients have already undergone pharmacotherapy but have not remitted. METHODS: Eligible participants were aged between 20 and 75 years and met the criteria for panic disorder/agoraphobia or social anxiety disorder specified in the DSM-IV. They were randomly assigned to either the MBCT group (n = 20) or the wait-list control group (n = 20). The primary outcome was the difference in mean change scores between pre- and post-intervention assessments on the State-Trait Anxiety Inventory (STAI). The outcome was analyzed using an intent-to-treat approach and a mixed-effect model repeated measurement. RESULTS: We observed significant differences in mean change scores for the STAI State Anxiety subscale (difference, -10.1; 95% confidence interval, -16.9 to -3.2; P < 0.005) and STAI Trait Anxiety subscale (difference, -11.7; 95% confidence interval, -17.0 to -6.4; P < 0.001) between the MBCT and control groups. CONCLUSION: MBCT is effective in patients with anxiety disorders in secondary-care settings where the vast majority of patients are treatment-resistant to pharmacotherapy.

Mediators of Change in Capnometry Guided Respiratory Intervention for Panic Disorder.

Capnometry guided respiratory interventions have shown promising results in the treatment of panic disorder, but mechanisms of change are not yet well-understood. The current study examined changes in end-tidal carbon dioxide (ETCO2), anxiety sensitivity, and perceived control as mediators of panic symptom change. Sixty-nine adults with panic disorder received 4 weeks of respiratory training, and panic symptom severity and potential mediators were assessed at Pre-treatment, Mid-treatment, Post-treatment, 2-month follow-up, and 12-month follow-up. Multilevel mediation analyses showed that changes in perceived control significantly mediated changes in panic disorder severity and that for individuals who were hypocapnic at pre-treatment, ETCO2 was a significant mediator of symptom outcome. Findings provide further evidence that changes in perceived control, and improvements in respiratory dysregulation for hypocapnic individuals specifically, underlie symptom improvement from capnometry guided respiratory intervention for panic disorder.

Transtorno de ansiedade e tratamento homeopático (relato de caso) / Anxiety disorder and homeopathic treatment (case report)

Trabalho realizado a partir do relato de caso clínico de uma jovem com diagnóstico de Transtorno de Ansiedade (Transtorno de Pânico em co-morbidade a Transtorno de Ansiedade Generalizada), os quais implicavam sofrimento emocional e significativas limitações para esta paciente. O autor propôs o tratamento e condução do caso de acordo com os fundamentos do tratamento homeopático clássico, com resultado bastante favorável. São comentados detalhes do tratamento homeopático realizado, o qual mostrou-se como alternativa eficaz ao tratamento psiquiátrico alopático convencional. Conclui citando que a abordagem homeopática se mostrou relevante ao reduzir os sintomas ansiosos gerais da paciente e trazer importante qualidade de vida e retomada da funcionalidade para a mesma. (AU)

Twelve-Month Outcomes Following Successful Panic-Focused Psychodynamic Psychotherapy, Cognitive-Behavioral Therapy, or Applied Relaxation Training for Panic Disorder.

OBJECTIVE: Given the chronic, episodic nature of panic disorder, it is important to examine long-term outcomes of patients who respond well to various psychotherapies. METHOD: Out of 116 patients with DSM-IV panic disorder who evidenced a ≥ 40% reduction in panic and avoidance symptoms on the Panic Disorder Severity Scale (PDSS) after 12-14 weeks of panic-focused psychodynamic psychotherapy, cognitive-behavioral therapy, or applied relaxation training as part of a 2-site randomized controlled trial conducted between January 2007 and July 2012, 91 patients provided at least 1 PDSS datapoint during follow-up. Patients were assessed at each of the 12 following months using the PDSS, the Sheehan Disability Scale (SDS), and the Hamilton Depression Rating Scale (HDRS) and twice during the follow-up period with the Anxiety Disorders Interview Schedule. RESULTS: Patients with panic disorder who responded to 1 of 3 treatments maintained their gains on the PDSS, SDS, and HDRS with no differences by condition in rates of change over the follow-up period (all P values ≥ .20). Similarly, 57% of improved patients did not have a panic disorder diagnosis by the end of 1 year, regardless of the treatment received. No differences in rates of panic disorder diagnosis were found across treatment conditions at either 6 months or 12 months (all P values ≥ .78). Results should be interpreted in light of the fact that patients giving data at follow-up experienced lower symptom levels at treatment termination than those not providing data. CONCLUSIONS: Improvement in any of the 3 treatments examined in this trial was largely maintained for a year following the end of therapy. Future treatment development could focus on factors to increase the level of response in the active phase of therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00353470.